Natural cytotoxicity in man: activity of lymph node and tumor‐infiltrating lymphocytes

101

Human malignant neoplasms not infrequently reveal mononuclear cell infiltrates which have features in common with immune-associated inflammatory reactions (Underwood, 1974). Although there is limited evidence for tumourrelated functional activity in the infiltrating leucocyte compartment (see Haskill, 1983), the relationship of the phenomenon at a functional or histological level to biological behaviour remains largely obscure.The majority of solid human neoplasms are characterised by marked cellular heterogeneity and any provisional assignment of in situ function will require the elucidation of the heterogeneity and microanatomical distribution of potential leucocytic effector cells relative to the tumour population. Such an analysis must also extend to the neoplastic *Present address:

Section: Monoclonal Antibodiessupporting

confidence: 79%

Expression of major histocompatibility antigens and leucocyte infiltration in benign and malignant human breast disease

Whitwell¹,

Hughes²,

Moore³

et al. 1984

101

“…In general, NK-cell function was markedly depressed in human tumours (Vose et al, 1977a;Totterman et al, 1980;Mantovani et al, 1980a;Haskill et al, 1982b). Specifically cytotoxic T cells have only been detected in a few instances (Vose et al, 1977b;Werkmeister et al, 1979) suggesting that effector-cell function may be difficult to maintain in situ.…”

Section: Discussionmentioning

confidence: 99%

Mononuclear-cell infiltration in ovarian cancer. III. Suppressor-cell and ADCC activity of macrophages from ascitic and solid ovarian tumours

Haskill¹,

Koren²,

Becker³

et al. 1982

Summary.-Macrophages have been isolated from ascitic and collagenase -dispersed tumours from patients undergoing surgery for ovarian cancer. Macrophages were present in varying proportions in both sites, though the ratio of macrophages to tumour cells was higher in ascites. Marked variation in size (as detected by sedimentation velocity) and cytochemical markers in the macrophages was noted. Highly enriched macrophage fractions were isolated from the ascites and collagenasedispersed solid tumours by a combination of sedimentation velocity and selective EA RFC or adherence techniques. Suppressor activity in the PHA assay was detected in tumour macrophages (4/10 giving>50% inhibition), ascitic macrophages (1/15) and blood monocytes (2/7). Lymphocyte fractions from tumours were unresponsive to PHA and failed to suppress the blood response. Suppressor activity was also present in the purified tumour-cell fraction of 6/14 patients.ADCC activity was tested in a few patients. When the activity was determined against the SB target cells, tumour-derived macrophages were inactive, whereas the ascitic fraction showed low but significant activity which averaged much lower than patient blood values. The ADCC assays carried out with the CRC target cell indicated activity within the range of patient blood values in 4/4 ascites and 2/4 tumour macrophage fractions.Cytotoxicity was also assessed against co-purified autologous tumour cells. Although activity was detected in many of the tests, the results seemed to reflect target cell sensitivity. There appeared to be a correlation between cytotoxicity with test macrophages and normal blood mononuclear cells.The results indicate that the cytochemical heterogeneity and the variation in size between macrophage fractions is associated with a spectrum of activities.WE HAVE INITIATED a study of immune competence of the various inflammatory cell types infiltrating primary solid and ascitic ovarian tumours. In the first paper (Haskill et al., 1982a) we outlined the methods used to isolate these cells and characterized the cell markers associated with infiltrating cells from these tumours. Two classes were characterized; 1 sedimented at < 6 mm/h and was similar in size to most blood mononuclear cells; the other was composed of larger, strongly adherent macrophages distinct from blood monocytes, which sedimented with the tumour cells. In the second communication (Haskill et al. 1982b) we investigated effector-cell functions (PHA, ADCC and NK) associated with blood and bloodequivalent inflammatory cells present in both ascitic and solid tumours. The data indicated that all tumour-derived effector-cell tests were markedly depres-

“…Enriched preparations of ascitesassociated lymphocytes were obtained by stepwise density and velocity separations similar to those used by Vose et al (1977) followed by repeated adherence steps or discontinuous Ficoll-Hypaque gradients. The percentage of lymphoid cells forming E RFC (39%) averaged less than that in either blood from patients or normal blood.…”

Section: Proportions Of Inflammatory: Tumour Cells In Ascites and Tummentioning

confidence: 99%

Mononuclear-cell infiltration in ovarian cancer. I. Inflammatory-cell infiltrates from tumour and ascites material

Haskill¹,

Becker²,

Fowler³

et al. 1982

Malignant effusions and tumour tissue obtained at surgery provided material for a study of the prognostic value of the various inflammatory cells in the prognosis of human ovarian cancer. Ascitic fluids predominantly contained inflammatory cells; tumour cells, both singly and in clusters, were a minor component. Tumour cells were usually in excess in dispersed solid material. Some patients had significant proportions of lymphocytes and macrophages in their solid tumour, and these patients invariably responded to therapy. Sedimentation-velocity separation at unit gravity provided tow populations of inflammatory cells. One consisted of mononuclear cells similar in size to those in the patients blood: the other consisted of one or more large macrophage populations, distinct in morphology and enzymatic markers from both blood monocytes and each other. T lymphocytes were enriched in ascites fractions (78%) and in the tumour-derived mononuclear fraction (71%) compared to patient blood (60%). The T-cell subset characterized by ANAE reactivity was markedly depleted in the tumour-infiltrating fraction (17%) compared to patient blood (62%) or patient blood (51%). Esterase-positive monocyte-like cells were more frequent in the tumour-infiltrating fraction (17%) than ascites (7%) or blood (12%). B lymphocytes were infrequent in solid tumours and difficult to assess in ascites. Histiocyte-like macrophages were present in the higher-velocity tumour-cell containing fractions of both solid and ascitic material. The variation in infiltrating cells between patients and between tumour and ascites of the same individual was marked.